RU2355383C2 - Microbial collagenase makeup preparation - Google Patents

Abstract

FIELD: medicine; cosmetology.

SUBSTANCE: makeup preparation for callous skin removal, wrinkle smoothing contains a microbial enzyme composition (ultralysine) recovered from collagenase and neutral proteases as a base active source, and also essences, glycerine, monoglycerides, stearin, triethanolamine, fats, aromatiser and water.

EFFECT: makeup preparation is characterised with moistening, antimicrobial, stimulating and antiallergic action.

3 ex, 1 tbl

Description

The invention relates to complex means for the care of coarsened skin of the legs and hands, rejuvenation of the skin of the face, smoothing wrinkles.

Various effective skin care cosmetics are known containing natural biologically active substances of animal and vegetable origin.

So, in the composition of a number of cosmetic compositions, along with traditional components, extracts and hydrolysates of plant and animal tissues were introduced [1, 2]. To improve the condition of dry, aging skin, prevent the formation of wrinkles, creams containing retinol, vitamin A acids and their derivatives are proposed [3, 4]. The restoration of firmness and elasticity of rough skin can be achieved using other compositions, for example, a cream containing vitamin A, hinokitiol and epidermal lipid [5].

Cosmetic creams containing enzymes of microbial or animal origin are also known. This series includes, for example, an agent that includes a neutral protease, elastase and collagenase, carboxypepsidase, leucine aminopeptidase, and subtilin-like protease [6].

The disadvantage of this composition is its toxic and allergic effects on the human body, due to the presence of elastase [7], which makes it impossible to use it for a long time.

Closest to the claimed invention and selected as a prototype is a cosmetic product containing crab collagenase as the main component of the enzyme preparation, and containing sea buckthorn or fir oil and propolis extract as biologically active additives in the following ratio, wt.%: Enzyme preparation 0.001-0.05; sea buckthorn or fir oil 0.2-5.0; propolis extract 0.1-10.0; polyethylene oxide gel; water the rest [8].

The disadvantage of the prototype is that the crab collagenase contained in its composition is not separated from the proteases of fibrinolytic action, despite the complex and expensive production technology. The fibrinolytic and thrombolytic properties inherent in the preparation can cause undesirable effects when applied to the skin. In addition, crab collagenase, unlike microbial collagenases, is not able to hydrolyze collagens until they are completely dissolved [9].

The objective of the proposed technical solution is the creation of a new effective cosmetic product with a necrolytic property for skin care, which provides a softening, regenerating, anti-aging effect on the skin due to the presence of microbial collagenase and a neutral protease (ultralizine preparation) in the composition, which was obtained more simply and cheapened way than collase (prototype), as well as not having fibrinolytic effect.

This task is achieved in that the proposed skin care product, including an enzyme preparation and targeted cosmetic additives, according to the invention contains collagenase and a neutral protease (ultralizine) as an enzyme preparation, and as an emollient contains olive oil, cosmetic stearin, triethanolamine, distilled monoglycerides, methyl and propyl ethers, perfume and water in the following ratio of components, wt.%:

Ultralizin TU 9336-001-11684510-03 9.0-11.0 olive oil FS-42-821-730ST 18-196-74 12.0-17.0 distilled monoglycerides TU 10-04-02-42-89 3,5-5,5 confectionery fat OST 18-197-84 4,5-6,0 cosmetic stearin TU 18-17 / 01-83 1,5-3,5 lanolin 1.5-2.5 distilled glycerin GOST 6824-76 1.5-2.5 triethanolamine TU 6-09-2448-91 0.6-0.9 perfume TU 64-19-149-92, TU 18 308757-94 0.4-0.6 paraoxybenzoic methyl ester acids TU 64-19-82-91 0.1-0.4 paraoxybenzoic propyl ester acids TU 64-19-83-91 0.1-0.3 water rest

The proposed composition has a wide spectrum of action, including active necrolytic, improves the condition of rough skin, promotes its rejuvenation.

The enzyme preparation ultralizine was isolated from a non-pathogenic strain of actinomycete Streptomyces lavendulae [10] using an environmentally friendly, affordable and cheapened technology. The enzyme preparation contains a stabilizer and remains active at temperatures from 0 degrees to + 10 degrees Celsius for two to three years. It is non-toxic, the test dose is 180 units of the enzyme preparation per 0.5 ml of water for injection per mouse (GF XI, issue 2, p.182). Moreover, according to the requirements of TU 9336-001-11684510-03, the drug ultralizin has a collagenolytic activity of at least 750 units and not more than 2000 KEA in 1 ml, pH from 5.0 to 7.0, storage conditions in a dark place at temperature from + 2 ° С to + 8 ° С, shelf life 3 years.

The proposed cosmetic product is prepared as follows. According to the recipe, all components except the enzyme preparation are loaded into the stirred tank reactor, heated to 100 degrees Celsius, then cooled to 40 degrees Celsius, the enzyme preparation and perfume are added, mixed, packaged in containers and stored at a temperature not exceeding + 10 degrees Celsius. The shelf life of the product is two years.

The invention is illustrated by the following examples in which the constituent components were used in various concentrations.

Example 1. A cosmetic product has the following component composition, wt.%:

enzyme preparation 8.0 olive oil 10.0 cosmetic stearin TU 18-17 / 01-83 1,0 triethanolamine TU 6-09-2448-91 0.5 distilled monoglycerides TU 10-04-02-42-89 2.0 confectionery fat OST 18-197-84 3,5 lanolin 0.8 distilled glycerin GOST 6824-76 0.8 paraoxybenzoic acid methyl ester TU 64-19-82-91 0.05 paraoxybenzoic acid propyl ester TU 64-19-83-91 0.05 perfume TU 64-19-149-92, TU 18 308757-94 0.3 water rest

Example 2. The cosmetic product has the following component composition, wt.%:

enzyme preparation 9.0 olive oil 12.0 cosmetic stearin TU 18-17 / 01-83 1,5 triethanolamine TU 6-09-2448-91 0.6 distilled monoglycerides TU 10-04-02-42-89 3,5 confectionery fat OST 18-197-84 4,5 lanolin 1,5 distilled glycerin GOST 6824-76 1,5 paraoxybenzoic acid methyl ester TU 64-19-82-91 0.1 paraoxybenzoic acid propyl ester TU 64-19-83-91 0.1 perfume TU 64-19-149-92, TU 18 308757-94 0.4 water rest

Example 3. The cosmetic product has the following component composition, wt.%:

enzyme preparation 12.0 olive oil 18.0 cosmetic stearin TU 18-17 / 01-83 4.0 triethanolamine TU 6-09-2448-91 1,0 distilled monoglycerides TU 10-04-02-42-89 6.0 confectionery fat OST 18-197-84 7.0 lanolin 3.0 distilled glycerin GOST 6824-76 3.0 paraoxybenzoic acid methyl ester TU 64-19-82-91 0.5 paraoxybenzoic acid propyl ester TU 64-19-83-91 0.5 perfume TU 64-19-149-92, TU 18 308757-94 0.8 water rest

In all cases, films soaked in a 10% solution of sodium lauryl sulfate were applied to the coarse feet. Films were removed after 3 hours and the treated areas were washed with water. Then, the samples of the compositions shown in examples 1, 2 and 3, in the form of ointment in equal amounts, were applied to the test areas of the roughened skin of the legs three times a day. After 3 and 7 days, the test areas of coarsened skin were examined with the naked eye, then the moisture content in the stratum corneum was measured to evaluate the improvement using a SKICON-200 skin layer stratum corneum moisture measuring instrument, IBS Corporation. The research results are presented in table 1.

Thus, in Example 1, when using a cosmetic composition, good non-political, emollient and tonic effects on the skin were not observed.

In Example 2, with the ratio of components used, the action of the enzyme complex was manifested more efficiently. In Example 3, with the concentration of ingredients used, the enzyme preparation “Ultralysin” exhibits the highest biological activity, completely hydrolyzing collagen. In combination with other components, this leads to the best necrolytic, softening and tonic effect of the proposed cosmetic products for the skin.

In another experiment, the proposed cosmetic product in the composition presented in Example 3 was studied in a group of 5 women aged 45 to 50 years. The cosmetic product was applied to the face twice a day in the morning and in the evening for a month and the condition of their skin was evaluated visually. The research results showed an improvement in skin firmness and elasticity, smoothing wrinkles, softening, and the absence of irritation and allergies.

The proposed cosmetic product was subjected to experimental clinical study according to the generally accepted methodology. As a result of tests, it was found that this drug does not have a general toxic, local, skin-resorptive and sensitizing effect.

The study of the irritating and sensitizing effect of the cream was carried out on sex and age rats of both sexes, weighing 200-220 g, located on the usual laboratory diet of vivarium.

There was no negative effect on the general condition of animals, their weight, behavior, condition of the coat and skin.

Clinical trials of the cream were conducted on 30 patients aged 16 to 78 years for 1.5 months.

The first stage of clinical trials is the identification of individual skin tolerance to the effects of the cream (24 and 48 hours). No individual sensitivity to the drug was detected in all patients.

A noticeable improvement in skin status was observed in 10 patients on day 7, in 16 patients on day 12 and in 4 patients on day 20.

All patients tolerated the cream well, undesirable effects and concomitant pathology were not observed.

Biochemical studies (blood tests, urine tests) in all patients both before and after applying the cream were within normal limits.

Industrial applicability.

The invention can be used in the cosmetic and medical industries.

Information sources

1. AK61K 7/15, 7/42, 7/44, 31/16 patent US 4482537, 1984. Composition for skin care.

2. A61K 7/48, EP 0180968, 1986. Cosmetic preparation against wrinkles.

3. Takao Inoue "Function and safety of vitamin A and D" // Fragrance J. N45, 1980, pp. 44-48.

4. Yoshimaru Kumano et al., "Anti-wrinkle cosmetics // Fragrance J. 1989, No. 1, pp.40-45.

5. Patent RU 2275185 C2, A61K 8/18, A61K 8/92. Means for external use.

6. Copyright certificate No. 719630, IPC A61K 7/00, 1980.

7. Zweiman B. et al. Release of lactoferrin and elastase in human allergy skin reactions // T. Immunol 1990. vol. 144, No. 10, pp.3953-3960.

8. Patent RU 2089177 C1, A61K 7/48, 1997.

9. Lim D.V. et al. Purification and assay of bacterial collagenases // J. Microbiol. Methods, 1993, vol. 18, pp. 241-253.

10. Patent RU 2075219, 03/10/97.

Table 1 Tests for the coarsening of the skin of the foot Days after application Naked eye assessment The percentage of moisture in the stratum corneum Example 1 Example 2 Example 3 Example 1 Example 2 Example 3 Source Rough skin Rough skin Rough skin 0% 10.0% 0% In 3 days No change Slight improvement Significant improvement 10.0% 12.0% 14.8% In 7 days Slight improvement Slight improvement Removing the "corns" 13.4% 16.8% one hundred%

Claims (1)

Cosmetic product for removing coarsened skin areas, smoothing wrinkles, providing a moisturizing, antimicrobial, stimulating effect on the skin, containing an enzyme preparation and cosmetic additives, characterized in that it contains an ultralysin substance based on microbial collagenase as an enzyme preparation, and as cosmetic additives contains olive oil, distilled monoglycerides, confectionery fat, cosmetic stearin, lanolin, distilled glycerin, triethanolamine, perfume, methyl and propyl esters of paraoxybenzoic acid, water in the following ratio of components, wt.%:
ultralysin 9.0-11.0 olive oil 12.0-17.0 distilled monoglycerides 3,5-5,5 confectionery fat 4,5-6,0 cosmetic stearin 1,5-3,5 lanolin 1.5-2.5 distilled glycerin 1.5-2.5 triethanolamine 0.6-0.9 perfume 0.4-0.6 paraoxybenzoic acid methyl ester 0.1-0.4 paraoxybenzoic acid propyl ester 0.1-0.3 water rest